Use of a Polyurethane Foam as a Wound Dressing in Negative Pressure Therapy

ABSTRACT

A device for negative pressure wound therapy having a cover material for air-tight sealing of the wound space connected to a negative pressure source; and a wound dressing having an open-cell polyurethane foam. The open-cell polyurethane foam has special properties, in particular a tensile strength after three days of storage in bovine serum, measured in accordance with DIN 53571, between 80 kPa and 300 kPa. The open-cell polyurethane foam may be used as a wound dressing in negative pressure wound therapy.

This application is a continuation of application Ser. No. 13/213,214,filed Aug. 19, 2011, and claims priority to U.S. Provisional ApplicationSer. No. 61/375,085, filed Aug. 19, 2010, the disclosures of which areincorporated by reference herein.

BACKGROUND OF THE INVENTION

The invention relates to a device for negative pressure wound therapycomprising (a) a cover material for air-tight sealing of the woundspace; (b) as applicable a means for the connection of a negativepressure source and (c) a wound dressing comprising an open-cellpolyurethane foam, whereby the open-cell polyurethane foam has specialcharacteristics, in particular a tensile strength after three days ofstorage in bovine serum, measured in accordance with DIN 53571, between80 kPa and 300 kPa. The invention further relates to the use of said anopen-cell polyurethane foam as a wound dressing in negative pressurewound therapy.

A wound is defined as the separation of the coherence of tissues of theouter body of humans or animals. It can result in a loss of substance.

Devices for the negative pressure wound therapy are known in the priorart. For example WO 1993/009727 A1 describes a device to promote healingof the wound by the application of a negative pressure on the skin areawhich is wounded and the area surrounding the wound. The deviceaccording to WO 1993/009727 A1 comprises a negative pressure device togenerate the negative pressure, an air-tight cover of the wound whichhas a functional connection with the negative pressure device, as wellas a wound dressing for positioning on the wound inside the air-tightcover.

Devices for the negative pressure wound therapy are commerciallyavailable, for example the V.A.C.® device from the company KCI.Commercially available devices often use a wound dressing which containsan open-cell polymer foam such as polyvinyl alcohol (PVA) orpolyurethane (PU).

The commercially available foam dressings are compressed to a differentdegree, depending on the negative pressure applied. This can cause aconstriction of the passages necessary for the removal of the woundexudate. Adhesion of the foam with the wound can also occur. Newlyformed tissue can grow into the wound. This problem is a familiarcomplication in the negative pressure therapy of wounds (FDA complaintdata base). In order to solve this problem, additional wound contactlayers are often introduced between the foam and the wound, for examplea film (see, for example, WO2001/85248). However, these additional woundcontact layers can reduce the passage of wound exudate.

When the wound dressing is to be changed, elaborate measures have to betaken to remove adhered foam, for example by rinsing with Ringer'ssolution. Tissue which has grown into the foam can lead to a tissuetraumatization when the wound dressing is removed and thus delay thehealing process.

When conventional wound dressings are used, particles of foam can alsoenter the wound. These can irritate the wound and delay the healingprocess. This problem is aggravated if the wound dressing is cut to thesize of the wound before being applied, as this results, in particular,in loose foam particles at the cut edges.

BRIEF SUMMARY OF THE INVENTION

It is the object of the present invention to further improve negativepressure wound therapy and to overcome the disadvantages of the priorart. The invention provides devices and methods for negative pressurewound therapy, with which a therapy can be carried out as effectivelyand gently as possible. In particular, the invention is aimed atpreventing the build-up of foam particles in the wound.

Unexpectedly, the objects could be solved by the use of a wound dressingcomprising a special polyurethane foam. In particular, it was found thatit was possible to simulate the conditions prevailing in negativepressure therapy by the storage of the polyurethane foam in bovineserum. If the polyurethane foam is selected in such a way that afterthree days of storage in bovine serum it has an advantageous tensilestrength, this leads to a surprisingly sharp reduction of undesired foamparticles in the wound. It was also found that it is possible to obtainpolyurethane foams which solve the aforementioned objects unexpectedlyadvantageously if certain other physical parameters are present and thestarting materials are appropriately selected.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 shows a schematic view (side view) of the device in accordancewith the present invention.

FIG. 2 illustrates the determination of undesired foreign particles inwounds in accordance with Example 2.

FIGS. 3 and 4 illustrate the histological examination of a wound treatedwith the inventive foam A showing only little inflammatory foci (IF) andthat the inflammatory foci show only minimal neutrophil infiltration.

FIGS. 5 and 6 illustrate that there are more areas with inflammatoryactivity in the granulation tissue of a wound treated with thecomparative foam B, and that the inflammatory that the foci (IF) consistof foreign body giant cells, neutrophil granulocytes and lymphocyticcells.

DETAILED DESCRIPTION OF THE INVENTION

The object of a first aspect of the invention is, therefore, a devicefor negative pressure wound therapy comprising

(a) a cover material for air-tight sealing of the wound space;

(b) as applicable, a means for the connection of a negative pressuresource; and

(c) an open-cell polyurethane foam as a wound dressing, obtainable byreaction of a mixture comprising the components

(i) polyisocyanate,

(ii) polyol, in particular polyester polyol,

(iii) blowing agent, and

(iv) catalyst,

whereby the open-cell foam, after three days of storage in bovine serum,preferably has a tensile strength, measured in accordance with DIN53571, between 80 kPa and 300 kPa.

The object of a second aspect of the invention is, therefore, a devicefor negative pressure wound therapy comprising

(a) a cover material for air-tight sealing of the wound space;

(b) as applicable, a means for the connection of a negative pressuresource; and

(c) an open-cell polyurethane foam as a wound dressing, obtainable byreaction of a mixture comprising the components

(i) polyisocyanate,

(ii) polyol, in particular polyester polyol,

(iii) blowing agent, and

(iv) catalyst,

whereby the open-cell polyurethane foam preferably has an airpermeability of 1,000 to 8,000l/(m²sec), measured in accordance with DINEN ISO 9237.

The object of a third aspect of the invention is, therefore, a devicefor negative pressure wound therapy comprising

(a) a cover material for air-tight sealing of the wound space;

(b) as applicable, a means for the connection of a negative pressuresource; and

(c) an open-cell polyurethane foam as a wound dressing, obtainable byreaction of a mixture comprising the components

(i) polyisocyanate, selected from MDI, PMDI, TDI and/or HDI,

(ii) polyester polyol, which is preferably obtainable by reaction of adicarboxylic acid with 4 to 8 carbon atoms with a dialcohol with 2 to 6carbon atoms, and/or preferably has a weight average molecular weight of500 to 4.000 g/mol,

(iii) blowing agent, and

(iv) catalyst.

The invention also includes any combinations of the cited aspects.

A further object of the invention is the use of the open-cellpolyurethane foam (c) described above in the three aspects, e.g. the useof an open-cell polyurethane foam which has a tensile strength afterthree days of storage in bovine serum, measured in accordance with DIN53571, between 80 kPa and 300 kPa, as a wound dressing for or innegative pressure wound therapy.

The new device in accordance with the present invention or the use ofthe wound dressing in accordance with the present invention isdistinguished by several unexpected advantages.

In particular, by selection of the characteristics of the foam it waspossible to advantageously reduce the number of undesirable particlesentering the wound.

The use of the wound dressing in accordance with the present inventionalso improved the atraumatic characteristics so that a negative pressuretherapy was possible without additional wound contact layers.

The wound dressing in accordance with the present invention allowsadequate drainage of wound exudates, feels relatively pleasant and thusleads to an increase in patient compliance (observance of the therapyinstructions by the patient).

The components (a) to (c) of the device in accordance with the presentinvention are described in the following.

The device in accordance with the present invention comprises a covermaterial (a) for air-tight sealing of the wound space. The wound spaceis regarded as the wound and the area surrounding the wound. “Air-tightsealing” does not mean that there is no exchange of gas between thewound space and its surroundings. Rather, “air-tight sealing” in thiscontext means that, taking into account the vacuum pump used, thenegative pressure necessary for the negative pressure wound therapy canbe maintained. This means that cover materials can also be used whichhave a slight degree of gas permeability as long as the negativepressure necessary for the negative pressure wound therapy can bemaintained.

In a preferred embodiment of the invention, the cover material for theair-tight sealing of the wound includes a water-insoluble polymer, or ametal foil. The cover material preferably has a thickness of 10 μm to10,000 μm, in particular from 25 μm to 100 μm.

In a preferred embodiment of the invention, the cover material (a) is awater-insoluble polymer. Preferably the water-insoluble polymer has asolubility of 10 mg/l or less, more preferably of 1 mg/ml or less,particularly from 0.0001 to 1 mg/ml (determined in accordance with thecolumn elution method pursuant to EU Directive RL67-548EEC, Annex V,Chapter A6). Examples include polyurethane, polyester, polypropylene,polyethylene, polyamide or polyvinyl chloride, polyorganosiloxane(silicone), or a mixture thereof. The cited polymers are preferablyprovided in non-cellular form.

It has been demonstrated that the objects explained at the beginning canbe solved in a particularly advantageous manner using a cover materialwith a specific water vapor permeability. In a preferred embodiment, thecover material thus has a water vapor permeability of 100 to 2,500g/m²×24 h, more preferably from 500 to 2,000 g/m²×24 h, and even morepreferably from 800 to 1,600 g/m²×24 h, in particular from 1,050 to1,450 g/m²×24 h, determined in accordance with DIN EN 13726-2 at 23° C.and 85% relative humidity. In particular, the combination of a coverfilm (a) having the aforementioned water vapor permeability with anopen-cell polyurethane foam having the physical properties describedbelow is particularly advantageous.

The device in accordance with the present invention for negativepressure wound therapy comprises a means (b) for the connection of anegative pressure source, i.e. a means for the generation of a negativepressure in the wound space. In a preferred embodiment, this is a means(b) for the functional connection of the wound space with a negativepressure source outside of the cover material so that a negativepressure can be generated in the wound space and fluids can be suckedout of the wound space.

The expression “negative pressure in the wound space” in the context ofthe invention describes an air pressure which is lower inside the wounddressing compared to the atmospheric pressure. “Within the wounddressing” refers to the cavity formed between the cover material and thewound.

The pressure difference between the air pressure inside the wounddressing and the atmospheric pressure is stated in the context of theinvention in mm Hg (millimeters of mercury), as this is the conventionin negative pressure therapy. 1 mm Hg corresponds to one torr or 133.322Pa (Pascal). In the context of the invention, the negative pressure,i.e. the pressure difference between the pressure inside the wounddressing and the atmospheric pressure, is stated as a positive numericalvalue in mm Hg.

In one embodiment of the invention, the negative pressure is at least 25mm Hg up to a maximum of 250 mm Hg, preferably at least 50 mm Hg up to amaximum of 150 mm Hg. This negative pressure range has proved suitablefor wound healing. In a preferred embodiment of the invention, thenegative pressure is at least 80 mm Hg up to a maximum of 140 mm Hg,more preferably at least 120 mm Hg up to a maximum of 130 mm Hg.

The device in accordance with the present invention for negativepressure wound therapy preferably comprises, as set out above, a means(b) for connection of a negative pressure source, i.e. a means for thefunctional connection of the wound space with a negative pressure sourceoutside of the cover material.

The functional connection can be generated, for example, by a connectionline or by a negative pressure connector. Negative pressure connectorsare known to those skilled in the art as “ports”.

In one embodiment, the means (b) is a connection line, preferably atube, in particular a silicone drainage tube. The connection line can beducted through the cover material. Alternatively, the at least oneconnection line can be led under the edge of the cover material. In bothcases the penetration point must be sealed air-tight so that the desirednegative pressure can be maintained in the dressing.

In a further preferred embodiment, the means (b) is a negative pressureconnector (port) which can be fastened to one of the inner or outersides of the cover material, whereby the cover material has thecorresponding openings. In this embodiment it is also important toensure air-tight sealing either of the penetration opening (inside port)or the surface of the dressing (outside port). Sealing can be achieved,for example, with an adhesive foil, an adhesive paste or an adhesivestrip.

Alongside the components (a) and, optionally, (b) described above, thedevice in accordance with the present invention also has a component(c). The wound dressing (c) used in the device in accordance with thepresent invention is described in more detail in the following. All ofthe explanations on the wound dressing (c) refer not only to the devicein accordance with the present invention, but also to the method inaccordance with the present invention for the manufacture of the wounddressing and the use in accordance with the present invention of thewound dressing in negative pressure wound therapy.

The wound dressing (c) comprises of an open-cell polyurethane foam (PURfoam). Foams are usually materials with cells (open, closed, or both)distributed over their whole mass. Such materials thus usually have araw density (in accordance with DIN EN ISO 845), which is lower than thedensity of the basic substance.

A cell is an individual cavity formed in the manufacture of the foamwhich is partially or fully enclosed by the cell walls and/or cellstruts.

A closed cell is usually a cell which is completely enclosed by itswalls and has no connection via the gas phase with the other cells. Anopen cell is usually a cell which is connected with other cells via thegas phase. In the context of this application, the term open-cell meansthat in the polyurethane foam there is at least 60% open cells,preferably at least 90% open cells, even more preferably 98% open cells,in particular essentially 100% open cells relative to the total numberof cells. The open cell content of the polyurethane foam is usuallydetermined in accordance with

ASTM D 2856-87, procedure B.

The cell wall is usually taken to mean the wall enclosing the cell. Thecell wall can also be referred to as the cell membrane. The cell strutis usually taken to mean the area of the cell wall which separates morethan two cells. Cell struts are preferably at least 1.5 times thethickness, even more preferably at least twice the thickness of the restof the cell wall.

The open-cell polyurethane foam can be a reticulated foam or anon-reticulated foam. A reticulated foam is taken to mean a foam whichconsists largely of cell struts. In a reticulated foam, therefore, thecell walls are largely absent. The reticulation is usually carried outin a pressure chamber, e.g. a steel chamber. When the foam is introducedto the steel chamber, the air is sucked out (preferably from 50 to 100weight percent, more preferably from 70 to 99 weight percent) andreplaced by a combustion gas mixture, preferably by a mixture containinghydrogen and oxygen, in particular in a molar ratio of 2:1. When the gasmixture is ignited, the cell skins are torn by the resulting heat andthe pressure wave. There may also be at least a partial melting of thecell struts so that these are reinforced.

The foam (c1) usually has a cell number (=number of pores along astraight line per cm) of 3 to 40 cm⁻¹, preferably 5 to 25 cm⁻¹, morepreferably 7 to 18 cm⁻¹, even more preferably from 8 to 15 cm⁻¹. Thecell number is preferably determined by microscope.

In principle, the open-cell polyurethane should fulfill certain physicalrequirements. It has been demonstrated that the objects set out abovecan be solved unexpectedly advantageously if the polyurethane foam has aspecific tensile strength, a specific ductile yield and/or a specifichardness.

In accordance with the present invention, the polyurethane foam usuallyhas a tensile strength after three days of storage in bovine serumbetween 80 kPa and 300 kPa, preferably between 110 kPa and 250 kPa, morepreferably between 120 kPa and 230 kPa, even more preferably from 130 to220 kPa, especially preferably from 140 to 200 kPa, very especiallypreferably from 155 to 190 kPa and in particular from 160 to 185 kPa.

Bovine serum is known in the prior art. This is a serum gained frombovine blood. Preference is given to the use of the “Standard FetalBovine Serum” sold under the trade name of HyClone® by the companyThermo Scientific. In a preferred embodiment, the bovine serum usedessentially has the following composition and properties:

Protein content and other values Albumin 1.9 gm/dl Alkaline phosphatase213 mU/ml Blood urea nitrogen 12 mg/dl Creatinine 2.77 mg/dl Gammaglobulin 1.7 % tp Blood sugar (glucose) 107 mg/dl Glutamic oxaloacetictransaminase (SGOT) 152 mU/ml Glutamic pyruvic transaminase (SGPT) 37mU/ml IgG - nephelometer 0.14 mg/ml Lactate dehydrogenase 2,479 mU/mlOsmolality 312 mOsm/kg pH 7.18 Total bilirubin 0.4 mg/dl Total protein3.7 gm/dl Content of trace elements and iron Calcium 13.1 mg/dl Chloride99 mEq/l Inorganic phosphorus 9.6 mg/dl Iron 160 μg/dl Saturationconcentration (iron) 79 % Potassium >10.0 mEq/l Sodium 133 mEq/l Totaliron-binding capacity (TIBC) 201 μg/dl

The specimen to be measured is placed in bovine serum and immersed for 3days at 23° C. Then the tensile strength is determined in accordancewith DIN 53571. In the context of this application, the expression “inaccordance with DIN 53571” means that the tensile strength is determinedin accordance with this standard in principle, whereby, in deviationfrom the standard, the specimen immersed for three days in bovine serumis not completely dried out. Instead, the specimen is taken from thebovine serum and immersed in 1 liter of water to be rinsed. Then thetest body is squeezed out with cellulose paper. Also, in deviation fromthe standard, a rectangular test body is used with the dimensions10×12.5×75.

The tensile strength is measured by using a tensile strength testingdevice in accordance with EN ISO 527-1 [April 1996] by the company Zwick(Ulm). The following test parameters apply:

Test speed: 500 mm/min

Clamping length: 50 mm

Initial load: 0.1 N

Specimen width b0: 12.5 mm

Furthermore, the polyurethane foam (c) preferably has a ductile yield of150% to 700%, more preferably from 200% to 650%, even more preferablyfrom 240% to 340%, particularly 260% to 320%, measured in accordancewith DIN 53571 (Procedure 1, body A). In addition to this, thepolyurethane foam preferably has a hardness of 20 to 70 Shore A, morepreferably from 30 to 60 Shore A, even more preferably from 40 to 50Shore A, measured in accordance with DIN 53505, whereby the measurementwas taken at 23° C. on a slab-like, flat and smooth test body with athickness of 6 mm

It has also been demonstrated that the objects set out above can besolved unexpectedly advantageously if the polyurethane foam has aspecific air permeability. In a preferred embodiment the polyurethanefoam has an air permeability of 1,000 to 8,000 l/(m²sec), morepreferably from 1,500 to 6,000 l/(m²sec), even more preferably from2,000 to 5,000 l/(m²sec), especially preferably from 2,300 to 4,000l/(m²sec), and in particular from 2,400 to 3,300 l/(m²sec) measured inaccordance with DIN EN ISO 9237 (20 mm test thickness, 20 cm² test area,200 Pa differential pressure).

It has also been demonstrated that the objects set out above can besolved unexpectedly advantageously if the polyurethane foam displaysvisco-elastic behavior. This means that the behavior of the polyurethanefoam under strain looks like a combination of an elastic solid and aviscous fluid. The visco-elastic behavior can be characterized by atorsional vibration test in accordance with DIN 53445, Procedure A. Itis preferred that the foam, when determined in accordance with DIN53445, Procedure A at 23° C., has a mechanical loss factor of 0.1 to1.0, more preferably from 0.15 to 0.8, even more preferably from 0.2 to0.6.

It has also been demonstrated that the objects set out above can besolved unexpectedly advantageously if the foam (c) has a raw densitybetween 15 and 55 kg/m³, more preferably between 20 and 35 kg/m³, evenmore preferably between 22 and 30 kg/m³, in particular between 24 and 28kg/m³, measured in accordance with DIN EN ISO 845 (test body withdimensions 100 mm×100 mm×50 mm, conditioning for 24 h in a standardclimate (23° C., 50% relative humidity, 1013 mbar)).

Insofar as the relevant standards do not state otherwise, the tests aregenerally carried out at 23° C. and 50% relative humidity and at apressure of 1013 mbar.

Preferred embodiments of the usable polyurethane foams (c-PUR) areexplained below. The polyurethane foam is usually obtained by reactionof a curable mixture comprising the components

(i-PUR) polyisocyanate,

(ii-PUR) compounds reactive to isocyanate, in particular polyol,

(iii-PUR) catalyst,

(iv-PUR) blowing agent, and

(v-PUR) additives, as applicable.

Generally known aliphatic, cycloaliphatic and/or, in particular,aromatic polyisocyanates can be used as isocyanates (i-PUR). Forexample, diphenylmethane diisocyanate (MDI), in particular,4,4′-diphenylmethane diisocyanate (4,4′-MDI), mixtures of monomericdiphenylmethane diisocyanates and higher-nucleus homologues ofdiphenylmethane diisocyanate (polymeric MDI), tetramethylenediisocyanate (TMDI), hexamethylene diisocyanate (HDI), toluylenediisocyanate (TDI) or mixtures thereof can be used to produce thepolyurethanes.

Preference is given to MDI, in particular 4,4′-MDI and/or HDI. Thepreferably used 4,4′-MDI can contain small quantities, up to around 10weight percent, of allophanate or uretonimine-modified polyisocyanates.Small quantities of polyphenylene polymethylene polyisocyanate (PMDI)can also be used. The total quantity of these PMDI should not exceed 5weight percent of the isocyanate used.

The polyisocyanate component (i-PUR) is preferably used in the form ofpolyisocyanate prepolymers. These polyisocyanate prepolymers areobtainable by reaction of the polyisocyanates described above (i-PUR),for example at temperatures of 30 to 100° C., preferably at around 80°C., with a substoichiometric amount of the polyols (ii-PUR) describedbelow to form a prepolymer. The polyol-polyisocyanate ratio is selectedin such a way that the NCO content of the prepolymer is 8 to 28 weightpercent, preferably 14 to 26 weight percent, particularly preferably 17to 23 weight percent.

Polyols such as polyetherols and/or polyesterols are usually used ascompounds reactive to isocyanates (ii-PUR).

It is also possible to use polyether polyalcohols (referred to in thisapplication as “polyether polyols”) with an OH functionality of 1.9 to8.0, a hydroxyl number of 50 to 1,000 mg KOH/g and, as applicable, 10 to100% primary hydroxyl groups. These types of polyether polyols areknown, commercially available and based, for example, on startercompounds which can be reacted with alkylene oxides, for examplepropylene oxide and/or ethylene oxide, under generally known conditions.The content of primary hydroxyl groups can be achieved by eventuallyreacting the polyols with ethylene oxide. To produce the open-cell foam(c) it is preferable not to use polyether polyols.

Preference is given to the use of polyester polyols in the component(ii-PUR). The polyesterols (ii-PUR) are generally produced bycondensation of multifunctional alcohols, preferably diols, with 2 to 12carbon atoms, preferably 2 to 6 carbon atoms, with multifunctionalcarboxylic acids with 2 to 12 carbon atoms, preferably 4 to 8 carbonatoms. Examples of suitable acids include succinic acid, glutaric acid,adipic acid, phthalic acid, isophthalic acid and/or terephthalic acidand mixtures thereof. Adipic acid is especially preferred. Examples ofsuitable di- and multi-valent alcohols include ethanediol, diethyleneglycol, 1,4-butanediol, 1,5-pentanediol, and/or 1,6-hexanediol andmixtures thereof. 1,4-butanediol is especially preferred.

The reaction conditions of carboxylic acid and alcohol are usuallyselected in such a way that the resulting polyesterols do not have anyfree acid groups. The resulting polyesterols also generally have aweight average molecular weight (determined using gel permeationchromatography) of 500 to 3,500 g/mol, preferably of more than 1,000g/mol to 3,000 g/mol, in particular from 1,500 to 2,500 g/mol. Ingeneral, the polyesterols used have an average theoretical functionalityof 2.0 to 4, preferably of more than 2 to less than 3. The polyesterolsused also generally have an average OH number of 20 to 150, preferablyfrom 30 to 80.

In a preferred embodiment, the polyesterols used have a viscosity of 150mPa·s to 600 mPa·s, preferably from 200 mPa·s to 550 mPa·s, morepreferably from 220 mPa·s to 500 mPa·s, especially preferably from 250mPa·s to 450 mPa·s and in particular from 270 mPa·s to 350 mPa·s,measured in accordance with DIN 53 015 at 75° C.

The compounds (ii-PUR) can be mixed with chain extenders and/orcross-linking agents. The chain extenders are mainly 2-functionalalcohols with molecular weights from 60 to 499, for example ethyleneglycol, propylene glycol, butanediol-1,4, pentanediol-1,5, dipropyleneglycol and/or tripropylene glycol. The cross-linking agents arecompounds with molecular weights from 60 to 499 and 3 or more active Hatoms, preferably amines, and especially preferably alcohols, forexample glycerin, trimethylol propane and/or pentaerythrite.

In a preferred embodiment the component (ii-PUR) preferably contains (orconsists of) 0 to 25 weight percent, preferably 1 to 20 weight percent,chain extenders and/or cross-linking agents and 75 to 100 weightpercent, preferably 80 to 99 weight percent polyol(s), in particularpolyester polyol(s), relative to the total weight of the component(ii-PUR).

Compounds which accelerate the reaction of the component (i-PUR) withthe component (ii-PUR) can be used as catalysts (iii-PUR). These couldinclude, for example, tertiary amines and/or organo-metallic compounds,in particular tin compounds. The following compounds can be used, forexample, as catalysts: triethylene diamine, aminoalkyl and/oraminophenyl imidazoles and/or tin (II) salts of organic carboxylicacids. Catalysts are generally used in a quantity of 0.1 to 5 weightpercent relative to the weight of the component (ii-PUR).

Generally known chemically or physically active compounds can be used asblowing agents (iv-PUR). Water can be used preferably as a physicallyactive blowing agent, which, when reacted with the isocyanate groups,forms carbon dioxide. Examples of physical blowing agents include(cyclo)aliphatic hydrocarbons, preferably those with 4 to 8, especiallypreferably 4 to 6, and in particular 5 carbon atoms, partiallyhalogenated hydrocarbons or ethers, ketones or acetates. The amount ofblowing agents used depends on the desired density of the foams. Thedifferent blowing agents can be used individually or in any mixture witheach other. Special preference is given to the use of only water as ablowing agent, generally in a quantity of 0.1 to 5 weight percent, inparticular from 2.5 to 4 weight percent relative to the weight of thecomponent (ii-PUR). Physical blowing agents are preferably used in aquantity of <0.5 weight percent relative to the weight of the component(ii-PUR).

The reaction takes place as applicable in the presence of (v-PUR)auxiliaries and/or additives, for example fillers, cell regulators, cellopeners, surfactants, and/or stabilizers against oxidative, thermal ormicrobial decomposition or aging.

To produce polyurethane foams, the components (i-PUR) and (ii-PUR) aregenerally made to react with each other in such quantities that theequivalence ratio of NCO groups to the sum of the reactive hydrogenatoms (in particular to the sum of the OH groups) is 1:0.8 to 1:1.25,preferably 1:0.9 to 1:1.15. A ratio of 1:1 corresponds here to an NCOindex of 100. The desired open cell content of the polyurethane foam isgenerally achieved by a suitable selection as recognized by thoseskilled in the art of the components (i-PUR) to (v-PUR). As applicable,after setting the resulting PUR foam is reticulated. For moreinformation on this, reference is made to the explanations given above.

It has also been demonstrated that the objects set out above can besolved unexpectedly advantageously if the polyurethane foam (c) containssilver in the form of silver ions or in the form of atomic silver.Preferably, a silver coating is applied after production of thepolyurethane foam. Alternatively the silver can be added to the curablecomposition. Preferably, the polyurethane foam contains 0.000001 to 0.1weight percent, more preferably 0.0001 to 0.01 weight percent silverrelative to the total weight of the polyurethane foam.

It has also been shown that the objects described at the beginning couldnot always be solved satisfactorily with polyurethanes solely on thebasis of aliphatic starting materials. Rather, the use of aromaticstructural components (i-PUR and/or ii-PUR) proves advantageous. In apreferred embodiment the polyurethane foam (c) thus has a proportion ofaromatic compounds of 5 to 50%, more preferably from 10 to 45%, inparticular from 15 to 40%. The proportion of aromatic compounds isdetermined by the ratio of the weight of aromatic rings to the totalweight of the foam.

In a preferred embodiment of the invention, the open-cell polyurethanefoam has a thickness of 1 to 50 mm, in particular from 15 to 35 mm

The open-cell polyurethane foam can also be used in a dry conditionsoaked with an ointment base, in particular a triglyceride ointmentbase. An especially preferred ointment base contains:

20 to 90 weight percent, preferably 55 to 80 weight percenttriglycerides, in particular containing fatty acid residues selectedfrom caprylic acid, capric acid, lauric acid and/or stearic acid;

5 to 75 weight percent, preferably 15 to 45 weight percenttriglycerides, in particular containing fatty acid residues selectedfrom isostearic acid, stearic acid, 12-hydroxy-stearic acid and/oradipic acid; and

0 to 30 weight percent, preferably 5 to 20 weight percent polyethyleneglycol with a weight average molecular weight of 500 to 3,000 g/mol. Ina preferred embodiment the proportion of ointment base is 10 to 95weight percent, more preferably 30 to 92 weight percent, even morepreferably 45 to 90 weight percent, especially preferably 55 to 88weight percent, in particular 65 to 85 weight percent relative to thetotal weight of the foam and the ointment base.

The foam is preferably not soaked, for example, with an activationsolution (e.g. Ringer's solution). It is also preferred that theopen-cell polyurethane foam is not coated or impregnated with a siliconegel, e.g. a hydrophobic silicone gel.

The polyurethane foam can also contain substances with antimicrobialaction. Substances with antimicrobial action can include for example,substances with amino or imino groups. Substances with antimicrobialaction can also be antimicrobially active metal cations, in particularsilver cations, for example a complex of 1-vinyl-2-pyrrolidones withsilver cations. Other especially suitable substances with antimicrobialaction further include biguanide derivatives such as chlorhexidine orpolybiguanides such as polyethylene biguanide (PEB), polytetramethylenebiguanide (PTMB) or polyethylene hexamethylene biguanide (PEHMB). Anespecially preferred polybiguanide is polyhexamethylene biguanide (PHMBor polyhexanide). Other suitable substances with antimicrobial actionare polyguanidines such as polyhexamethylene guanidine (PHMG),N-octyl-1-[10-(4-octyliminopyridine-1-yl)decyl]pyridine-4-imine(octenidine), quaternary ammonium compounds such as benzalkoniumchloride or cetylpyridinium chloride, triazines such as1-(3-chloroallyl)-3,5,7-triaza-1-azonia-adamantan-chloride or theammonium compound taurolidine.

Preferably the open-cell polyurethane foam is impregnated or coated withthe aforementioned substances with antimicrobial action.

Substances with antimicrobial action are usually contained in thepolyurethane foam in a quantity of 0 to 30 weight percent, preferablyfrom 0.1 to 15 weight percent relative to the total weight of thepolyurethane foam.

In principle, the explanations of preferred embodiments of individualparameters of the polyurethane foam (c) must not be seen in isolation,but in combination with the explanations of preferred embodiments ofother parameters or in combination with the explanations of thesubstance compositions. Accordingly, the device in accordance with thepresent invention and its use in accordance with the present inventioncan be an open-cell foam (c) which,

after three days of storage in bovine serum, has a tensile strength of80 kPa to 300 kPa, preferably from 110 kPa to 250 kPa, more preferablyfrom 120 kPa to 230 kPa, even more preferably from 130 kPa to 220 kPa,especially preferably from 140 kPa to 200 kPa, most especiallypreferably from 155 kPa to 190 kPa and in particular from 160 kPa to 185kPa;

a ductile yield of 150% to 500%, more preferably from 200% to 380%, evenmore preferably from 240% to 340%, in particular 260% to 320%;

a mechanical loss factor of 0.1 to 1.0, more preferably from 0.15 to0.8, even more preferably from 0.2 to 0.6;

a hardness of 20 to 70 Shore A, more preferably from 30 to 60 Shore A,even more preferably from 40 to 50 Shore A;

a cell number (=number of pores along a straight line per cm) from 3 to40 cm⁻¹, preferably from 5 to 25 cm⁻¹, more preferably from 7 to 18cm⁻¹, even more preferably from 8 to 15 cm⁻¹;

a raw density between 15 and 55 kg/m³, more preferably between 20 and 35kg/m³, even more preferably between 22 and 30 kg/m³, in particularbetween 24 and 28 kg/m³; and/or

an air permeability of 1,000 to 8,000 l/(m²sec), more preferably from1,500 to 6,000 l/(m²sec), even more preferably from 2,000 to 5,000l/(m²sec), especially preferably from 2,300 to 4,000 l/(m²sec) and inparticular from 2,400 to 3,300 l/(m²sec);

and is preferably obtainable by reaction of a polyisocyanate (i),selected from MDI, PMDI and/or TDI, with a (ii) polyester polyol, whichis preferably obtainable by reaction of a dicarboxylic acid with 4 to 8carbon atoms with a dialcohol with 2 to 6 carbon atoms, whereby the (ii)polyester polyol preferably has a weight average molecular weight of 500to 4,000 g/mol; and/or

the open-cell polyurethane foam has a proportion of aromatic compoundsof 5 to 50%, more preferably from 10 to 45%, in particular from 15 to40%.

The present invention also comprises any combinations of the citedaspects. Accordingly, an especially preferred foam, for example afterthree-day storage in bovine serum, has a tensile strength between 155kPa and 190 kPa; a ductile yield of 260% to 320%; a cell number of 8 to15 cm⁻¹; a raw density between 24 and 28 kg/m³; and/or an airpermeability of 2,400 to 3,300l/(m²sec).

This foam is preferably obtainable by reaction of a polyisocyanate (i),selected from MDI, PMDI and/or TDI, with a (ii) polyester polyol, whichis preferably obtainable by reaction of a dicarboxylic acid with 4 to 8carbon atoms with a dialcohol with 2 to 6 carbon atoms, whereby the (ii)polyester polyol preferably has a weight average molecular weight of 500to 4,000 g/mol.

Furthermore, the invention provides a ready-to-use set for negativepressure wound therapy, including the device in accordance with thepresent invention, whereby the polyurethane foam is suitable as a wounddressing and is provided in a ready-to-use pack.

The object of the invention is thus a ready-to-use set for negativepressure wound therapy comprising

(a) a cover material for air-tight sealing of the wound space, i.e. thewound and the area surrounding the wound,

(b) as applicable, a means suitable for the connection of a negativepressure source, preferably a means for the functional connection of thewound space with a negative pressure source outside of the covermaterial in such a way that a negative pressure can be generated in thewound space and fluids can be drawn out of the wound space by suction,

and

(c) a wound dressing in a ready-to-use pack, comprising an open-cellpolyurethane foam which has the properties described above, e.g. atensile strength after three-day storage in bovine serum, measured inaccordance with DIN 53571, between 80 kPa and 300 kPa.

The wound dressing (c) included in the set as a ready-to-use pack shouldpreferably be provided in a damp-proof pack. Preferably the ready-to-usewound dressing is provided in sterile form, whereby especially radiationand/or ethylene oxide can be used for sterilization. The set can containfurther optional elements such as adhesive means to fix the dressing,sealing means to generate an air-tight seal of the dressing, pressuresensors, connection elements for pressure sensors, additional tubes,connectors for tubes, disinfectants, skin care products, pharmaceuticalpreparations or instructions for use. The set in accordance with thepresent invention preferably also contains scissors, pads and/orpincers, in particular in sterile form. Preferably the set also containsa ready-to-use negative pressure unit.

A further object of the invention is the use of the wound dressing (c)explained above for or in the negative pressure wound therapy. An objectof the invention is thus also the use of the special open-cellpolyurethane foam described above for the negative pressure therapy ofwounds, in particular as a wound dressing. In particular, the object ofthe invention is the use of an open-cell polyurethane foam which has atensile strength after three days of storage in bovine serum, measuredin accordance with DIN 53571, between 80 kPa and 300 kPa for thenegative pressure therapy of wounds, in particular as a wound dressing(c). All of the above explanations of preferred embodiments regardingthe component (c), i.e. the open-cell polyurethane foam, apply not onlyto the device in accordance with the present invention, but also to theuse of the device in accordance with the present invention.

Special advantages of the device in accordance with the presentinvention, the set in accordance with the present invention or the useor application in accordance with the present invention, arise when thewounds are burn wounds, wounds caused by mechanical trauma, woundscaused by exposure to chemicals, wounds caused by a metabolic disorder,wounds caused by a circulatory disorder or wounds caused by pressureulcers, particularly when these wounds are chronic wounds. Furthermore,wounds caused by diabetic foot ulcer can be treated particularlyadvantageously. In addition, wounds caused by radiation induced ulcercan be treated advantageously with the means of the present invention.

In a further preferred embodiment, the wound dressing (c) is providedfor use in negative pressure therapy in the treatment of a wound causedby a skin graft. The application includes the treatment of wounds causedby split-skin and full-skin transplants using negative pressure therapy.Advantageous effects arise due to the structure of the special open-cellpolyurethane foam, which preferably has a tensile strength after threedays of storage in bovine serum, measured in accordance with DIN 53571,between 80 kPa and 300 kPa, and due to the uniform distribution ofpressure. When the wound dressing (c) is used in the treatment of awound caused by a skin graft, the skin graft can be adequately fixedwhile avoiding undesired shear forces.

The wound dressing (c) described above can be used advantageously as awound dressing in the negative pressure therapy of pressure wounds inpatients with a body-mass index (BMI=body weight over height squared) ofless than 18.0, in particular with a body mass index of 14 to 17.5. Thisapplies in particular to patients aged over 60. The advantageous effectof the device in accordance with the present invention or the set inaccordance with the present invention is manifested in particular insuch patients.

Another object of the invention is a method for negative pressure woundtherapy, comprising the steps of

a) providing a device according to one of the claims 1 to 13;

b) applying the negative pressure dressing to the wound;

c) generating a negative pressure of 25 mm Hg to 250 mm Hg, preferably50 mm Hg to 150 mm Hg in the wound space for at least 30 minutes and upto a maximum of 7 days, preferably for at least 1 day and up to amaximum of 6 days.

FIGURES

FIG. 1: Schematic view of the device in accordance with the presentinvention (side view)

1 Wound surroundings (i.e. generally undamaged skin)

2 Air-tight cover material (a)

3 Wound dressing (c)=open-cell polyurethane foam

4 Negative pressure connector (port)

5 Negative pressure connection line

6 Collector

7 Negative pressure unit

8 Wound

The device in accordance with the present invention for negativepressure wound therapy is explained in more detail in FIG. 1. FIG. 1shows a schematic view (side view) of the device in accordance with thepresent invention. The device comprises an air-tight cover material (2),a means (4-5) for the functional connection of the wound space with anegative pressure source (7) outside of the cover material, and theopen-cell foam (3). The cover material (2) is fastened in the area ofthe wound surroundings (1), usually consisting of undamaged skin. Thesize of the cover material must be such that the cover material can befastened outside of the wound space in the area of the woundsurroundings (1). The cover material (2) can have different dimensionsand shapes, for example circular, oval or rectangular. It can also havean irregular shape matched to the individual wound. The cover material(2) is usually fastened in the area of the wound surroundings (1) andsealed air-tight. This can be achieved, for example, by providing anadhesive edge on the cover material (2). Alternatively, an adhesivesubstance can be applied either to the edge of the cover material (2)and/or the intact skin around the wound. This has the advantage that itis easier to match the cover material to the shape and size of thewound. In the preferred embodiment shown here, the negative pressureconnector (4) is attached to the outside of the air-tight cover material(2) facing away from the wound. In order to functionally connect thewound space with a negative pressure unit (7) outside of the covermaterial in this arrangement, there must be one or more openings passingthrough the cover material (2) in the proximity of the negative pressureconnector (4).

In a preferred embodiment of the invention the device for the negativepressure wound therapy includes no wound contact layer between the wounddressing (3) and the wound surface (8).

FIG. 2 illustrates the determination of undesired foreign particles inwounds in accordance with Example 2.

The invention is illustrated by the following examples.

EXAMPLE 1 Determination of the Tensile Strength

A foam in accordance with the present invention was produced and a foamcommercially available for negative pressure therapy was used as acomparison:

Foam A (in accordance with the present invention), obtainable byreaction of polyester polyol and isocyanate, tensile strength after drystorage in a standard climate 160 kPa, tensile strength after three daysof storage in bovine serum: 170 kPa.

Foam B (comparison), obtainable by reaction of polyether polyol andisocyanate, tensile strength after dry storage in a standard climate 115kPa, tensile strength after three days of storage in bovine serum: 72kPa.

EXAMPLE 2 Determination of Undesired Foreign Particles in Wounds

6 pigs were treated on 8 wounds each with a device for negative pressurewound therapy comprising either the foam A in accordance with thepresent invention from example 1 or the comparison foam B for 7 days. Asystematic diagram of the test set-up is shown in FIG. 2. FIG. 2 shows apig's back from above. S1 to S8 are the wounds covered with foam, 1 and2 represent a wound dressing of the foams A or B, each covering fourwounds. 3 and 4 are openings for connection with the negative pressuresystem. 5 is the head of the pig, 6 the tail.

When the treatment period ended, the wounds were examined for undesiredfoam particles. The result was as follows:

Foam in accordance with the present invention A: 0% of the woundscontained foam particles.

Comparison foam B: 25% of the wounds contained foam particles.

EXAMPLE 3 Histological Examination of Inflammatory Activity in Wounds

As described in Example 2, a foam A according to the present inventionand a comparative foam B were used as wound dressings.

Granulation tissues were examined histologically.

The histological examination of a wound treated with the inventive foamA shows only little inflammatory foci (IF), as illustrated in FIG. 3.The inflammatory foci show only minimal neutrophil infiltration, seeFIG. 4.

Contrary, there are more areas with inflammatory activity in thegranulation tissue of a wound treated with the comparative foam B, asillustrated in FIG. 5. The inflammatory foci (IF) consist of foreignbody giant cells, neutrophil granulocytes and lymphocytic cells, asillustrated in FIG. 6.

Consequently, using a foam according to the present invention isassociated with less inflammatory activity.

1. A device for negative pressure wound therapy comprising (a) a covermaterial for air-tight sealing of the wound space; (b) optionally, aconnector of a negative pressure source; and (c) an open-cellpolyurethane foam as a wound dressing, obtained by reaction of a mixturecomprising the components (i) polyisocyanate selected from the groupconsisting of diphenylmethane diisocyanate (MDI), mixtures of monomericdiphenylmethane diisocyanates and higher-nucleus homologues ofdiphenylmethane diisocyanate (polymeric MDI), tetramethylenediisocyanate (TMDI), hexamethylene diisocyanate (HDI), toluylenediisocyanate (TDI) and mixtures thereof, (ii) polyol, (iii) blowingagent, and (iv) catalyst, wherein the open-cell polyurethane foam has anair permeability of 1,000 to 8,000 l/(m²sec), measured in accordancewith DIN EN ISO
 9237. 2. The device in accordance with claim 1, whereinthe polyol is a polyester polyol.
 3. The device in accordance with claim1, whereby the (i) polyisocyanate is selected from the group consistingof MDI, PMDI and TDI.
 4. The device in accordance with claim 2, wherebythe (ii) polyester polyol is obtainable by reaction of a dicarboxylicacid with 4 to 8 carbon atoms with a dialcohol with 2 to 6 carbon atoms.5. The device in accordance with claim 2, whereby the (ii) polyesterpolyol has a weight average molecular weight of 500 to 4,000 g/mol. 6.The device in accordance with claim 1, whereby the open-cellpolyurethane foam has a ductile yield of 250% to 650%, measured inaccordance with DIN
 53571. 7. (canceled)
 8. The device in accordancewith claim 1, whereby the open-cell polyurethane foam has a raw densitybetween 15 and 30 kg/m³, measured in accordance with DIN EN ISO
 845. 9.The device in accordance with claim 1, whereby the open-cellpolyurethane foam has a proportion of aromatic compounds of 5 to 50%.10. The device in accordance with claim 1, whereby the open-cellpolyurethane foam has a hardness of 20 to 70 Shore A, measured inaccordance with DIN
 53505. 11. The device in accordance with claim 1,whereby the open-cell polyurethane foam has a cell number of 5 to 25cm⁻¹.
 12. The device in accordance with claim 1, whereby the open-cellpolyurethane foam displays visco-elastic behavior.
 13. The device inaccordance with claim 1, whereby the cover material (a) has a watervapor permeability of 100 to 2,500 g/m 2×24 h, measured in accordancewith DIN EN 13726-2.
 14. Use of an open-cell polyurethane foam as awound dressing for negative pressure wound therapy, whereby theopen-cell polyurethane foam is obtainable by reaction of a mixturecomprising the components (i) polyisocyanate selected fromdiphenylmethane diisocyanate (MDI), in particular, 4,4′-diphenylmethanediisocyanate (4,4′-MDI), mixtures of monomeric diphenylmethanediisocyanates and higher-nucleus homologues of diphenylmethanediisocyanate (polymeric MDI), tetramethylene diisocyanate (TMDI),hexamethylene diisocyanate (HDI), toluylene diisocyanate (TDI) ormixtures thereof can be used to produce the polyurethanes, (ii) polyol,in particular polyester polyol, (iii) blowing agent, and (iv) catalyst,and wherein the open-cell polyurethane foam has an air permeability of1,000 to 8,000 l/(m²sec), measured in accordance with DIN EN ISO 9237.15. Use in accordance with claim 14, whereby the wounds are burn wounds,wounds caused by mechanical trauma, wounds caused by exposure tochemicals, wounds caused by a metabolic disorder, wounds caused by acirculatory disorder, wounds caused by radiation induced ulcer, woundscaused by diabetic foot ulcer, or wounds caused by pressure ulcers. 16.A method for negative pressure wound therapy, said method comprisingdressing a wound with an open-cell polyurethane foam obtained byreaction of a mixture comprising the components (i) polyisocyanateselected from the group consisting of diphenylmethane diisocyanate(MDI), mixtures of monomeric diphenylmethane diisocyanates andhigher-nucleus homologues of diphenylmethane diisocyanate (polymericMDI), tetramethylene diisocyanate (TMDI), hexamethylene diisocyanate(HDI), toluylene diisocyanate (TDI) and mixtures thereof, which is usedto produce the polyurethane, (ii) polyester polyol, (iii) blowing agent,and (iv) catalyst, wherein the open-cell polyurethane foam has an airpermeability of 1,000 to 8,000 l/(m²sec), measured in accordance withDIN EN ISO
 9237. 17. The method of claim 16, wherein the polyisocyanateis 4,4′-diphenylmethane diisocyanate (4,4′-MDI).
 18. The method of claim16, wherein the wound is a burn wound, a wound caused by mechanicaltrauma, a wound caused by exposure to chemicals, a wound caused by ametabolic disorder, a wound caused by a circulatory disorder, a woundcaused by radiation induced ulcer, a wound caused by diabetic footulcer, or a wound caused by pressure ulcer.